Download Pneumococcal Septic Arthritis: Review of 190 Cases

MAJOR ARTICLE
Pneumococcal Septic Arthritis:
Review of 190 Cases
John J. Ross,1 Charles L. Saltzman,4 Philip Carling,3 and Daniel S. Shapiro2
1
Division of Infectious Diseases, Saint Elizabeth’s Medical Center, and 2Clinical Microbiology and Molecular Diagnostics Laboratory, Boston
Medical Center, Boston, and 3Department of Medicine, Carney Hospital, Dorchester, Massachusetts; and 4Department of Orthopedic Surgery,
University of Iowa, Iowa City
This article reports 13 cases of pneumococcal septic arthritis and reviews another 177 cases reported since
1965. Of 2407 cases of septic arthritis from large series, 156 (6%) were caused by Streptococcus pneumoniae.
Mortality was 19% among adults and 0% among children. Pneumococcal bacteremia was the strongest predictor
of mortality. At least 1 knee was involved in 56% of adults. Polyarticular disease (36%) and bacteremia (72%)
were more common among adults with septic arthritis caused by S. pneumoniae than among adults with other
causative organisms. Only 50% of adults with pneumococcal septic arthritis had another focus of pneumococcal
infection, such as pneumonia. Functional outcomes were good in 95% of patients. Uncomplicated pneumococcal septic arthritis can be managed with arthrocentesis and 4 weeks of antibiotic therapy; most cases of
pneumococcal prosthetic joint infection can be managed without prosthesis removal. A fatal case of septic
arthritis caused by a b-lactam–resistant strain of S. pneumoniae is also presented.
Pneumococcal septic arthritis is described as “rarely
encountered” [1] or “unusual” [2]. However, Streptococcus pneumoniae causes septic arthritis more often
than is generally thought. Ispahani et al. [3] last reviewed pneumococcal septic arthritis in this journal,
reporting 32 cases and reviewing 58 cases from large
series published since 1965. We present 13 previously
unreported cases and review 177 cases of pneumococcal
septic arthritis reported in the English-language literature since 1965 [3–59], emphasizing the frequency of
bacteremia and polyarticular disease among adults, the
absence of extra-articular infection in many patients,
and the emerging problem of pneumococcal antibiotic
resistance. We report 2 cases of pneumococcal prosthetic joint infection and a case of pneumococcal arthritis in an adult that was caused by a strain of S.
pneumoniae with high-level resistance to penicillin and
intermediate resistance to ceftriaxone.
PATIENTS AND METHODS
We identified 13 cases of pneumococcal septic arthritis
from the medical records of our institutions, Boston
Medical Center (formerly Boston City Hospital), the
University of Iowa Hospitals (Iowa City), Carney Hospital (Dorchester, MA), and Saint Elizabeth’s Medical
Center of Boston. Pneumococcal septic arthritis was
defined by isolation of S. pneumoniae from synovial
fluid or by pneumococcal bacteremia with purulent
joint fluid, positive results of Gram staining of joint
fluid, or an imaging study demonstrating sacroiliitis.
RESULTS
Received 21 August 2002; accepted 1 November 2002; electronically published
13 January 2003.
Reprints or correspondence: Dr. John J. Ross, Div. of Infectious Diseases, Saint
Elizabeth’s Medical Center, 736 Cambridge St., Boston, MA 02135 (jrossmd
@cchcs.org).
Clinical Infectious Diseases 2003; 36:319–27
2003 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2003/3603-0012$15.00
Epidemiology. Demographic and clinical characteristics of the 13 patients we report here are summarized
in table 1, and the clinical and laboratory findings for
our patients, along with 177 cases reported elsewhere
since 1965, are summarized in table 2. The mean age
of adults with pneumococcal septic arthritis for whom
Pneumococcal Septic Arthritis • CID 2003:36 (1 February) • 319
Table 1.
Patient
Demographic and clinical characteristics of 13 previously unreported patients with pneumococcal septic arthritis.
Sex, age
Affected
joint
Streptococcus
pneumoniae
serotype
Sample with
positive culture
results
Predisposing
factors
Other site of
infection
Therapy, outcome
1
M, 1 month
Elbow
NA
Blood, joint
Prematurity
None
I&D, 3 weeks iv antibiotics; cured
2
F, 2 years
Elbow
NA
Joint
None
None
Arthrocentesis, 1 week iv antibiotics, 2 weeks oral antibiotics;
cured
3
F, 43 years
Elbow
9N
Joint
EtOh, trauma
None
Arthrocentesis, 2 weeks iv antibiotics, 2 weeks oral antibiotics;
decreased ROM
4
M, 51 years
Knee, shoulder,
ankle, SC
NA
Blood, joint
Smoking, recent
URTI
Endocarditis
Arthrocentesis, 8 weeks iv antibiotics; MVR
5
M, 51 years
Knee
12F
Joint
EtOh, smoking
None
Arthrocentesis, 2 weeks iv antibiotics, 2 weeks oral antibiotics;
decreased ROM
6
F, 51 years
Shoulder
6A
Blood, joint
EtOh, smoking, RA
None
Signed out AMA; lost to follow-up
7
M, 52 years
Knee, shoulder
NA
Blood, joint
EtOh, trauma, CHF
None
I&D, 8 weeks iv antibiotics,
1 week oral antibiotics; cured
8
M, 60 years
Shoulder
23F
Blood, joint
EtOh, smoking,
gout
None
I&D, 6 weeks iv antibiotics; decreased ROM
9
M, 65 years
Knees
17F
Blood, joint,
CSF
CHF, DM, COPD,
CRI, EtOh
Pneumonia,
meningitis
Arthrocentesis, 4 weeks iv antibiotics; cured
10
M, 66 years
Wrists, ankles,
knee
NA
Blood, joint
EtOh, cirrhosis,
CHF, CRI
Pneumonia
Died of sepsis
11
F, 73 years
Hip prosthesis
NA
Blood, joint
OA, COPD
Pneumonia
Died of sepsis
12
F, 74 years
Knees
23F
Blood, joint,
CSF
MGUS, OA
Pneumonia,
meningitis
I&D, 6 weeks iv antibiotics; cured
13
F, 79 years
Hip prosthesis
NA
Blood, joint
CHF, COPD, OA
None
Arthrocentesis, 6 weeks iv antibiotics; infection suppressed with
indefinite oral antibiotics
NOTE. AMA, against medical advice; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CRI, chronic renal insufficiency; DM,
diabetes mellitus; EtOh, alcohol abuse; I&D, incision and drainage; MGUS, monoclonal gammopathy of undetermined significance; MVR, mitral valve replacement; NA, not available; OA, osteoarthritis; RA, rheumatoid arthritis; ROM, range of motion; SC, sternoclavicular; URTI, upper respiratory tract infection.
age data were available was 59 years. Most children with pneumococcal septic arthritis were !2 years old (62 [78%] of 80
children). Pneumococcal septic arthritis in adults was equally
common in men (53 [51%] of 104 adults) and women (51
[49%] of 104 adults). Septic arthritis was slightly more common
among boys (29 [60%] of 48 children) than among girls (19
[40%] of 48 children). Antecedent upper respiratory infection
occurred in 14 (18%) of 80 children and 11 (10%) of 105
adults. Five (6%) of 80 children and 6 (6%) of 105 adults
reported recent trauma to the affected joint. Fifty-six (93%) of
60 children and 43 (65%) of 66 adults presented with a temperature 138.0C.
Laboratory findings.
Serum leukocytosis (WBC count
9
111 ⫻ 10 cells/L) was observed in 41 (95%) of 43 children and
55 (61%) of 90 adults for whom WBC counts were available.
Gram staining of joint fluid showed S. pneumoniae in 14 (38%)
of 37 children and 61 (77%) of 79 adults. Cultures of joint
fluid for S. pneumoniae were positive in 70 (88%) of 80 children
and 82 (84%) of 98 adults. Joint fluid was usually purulent,
with a mean WBC count of 127,000 cells/mm3 (range, 5500–
362,000 cells/mm3). Differential counts showed a predominance of neutrophils, with a mean of 92% polymorphonuclear
320 • CID 2003:36 (1 February) • Ross et al.
leukocytes (range, 73%–100%). These values were similar for
adults and children.
Joint involvement. Most adults with pneumococcal septic
arthritis have knee involvement (table 3). Thirty-five (32%) of
108 adults had monoarticular involvement of a knee joint, and
26 adults with polyarticular septic arthritis had knee involvement. Therefore, 56% of adults with pneumococcal septic arthritis had involvement of at least 1 knee. Other adults with
monoarticular arthritis had involvement of the hip (7%), shoulder (6%), ankle (5%), or elbow (3%). Polyarticular disease was
more common among adults (36%) than among children (7%).
Among children, involvement of the hip joint was most common (24%), followed by involvement of the knee (21%), elbow
(18%), and ankle (15%).
Comorbid conditions and risk factors. Comorbid conditions and risk factors are summarized in tables 4 and 5. Most
adults and children 12 years old with pneumococcal septic
arthritis had underlying medical conditions. Such conditions
were present in 85% (92 of 108) of adults with pneumococcal
septic arthritis and 83% (15 of 18) of children aged 2–16 years.
However, only 10% (5 of 52) of children !2 years old had
comorbid conditions.
Table 2. Clinical findings and demographic characteristics for
190 patients (82 children and 108 adults) with pneumococcal septic arthritis.
Finding or characteristic
Children,
n/N (%)
Adults,
n/N (%)
Sex
Male
29/48 (60)
53/104 (51)
Female
19/48 (40)
51/104 (49)
14/80 (18)
11/105 (10)
Recent URTI (immediately
before onset of arthritis)
Antecedent trauma
5/80 (6)
6/105 (6)
Temperature 138C
56/60 (93)
43/66 (65)
0/80 (0)
14/105 (13)
Prosthetic joint
Pneumonia
2/80 (3)
38/105 (36)
Meningitis
3/80 (4)
16/105 (15)
Endocarditis
No extra-articular infection
0/80 (0)
6/105 (6)
75/80 (94)
53/105 (50)
Bacteremia
Without extra-articular infection
With extra-articular infection
42/45 (93)
35/75 (47)
3/45 (7)
40/75 (53)
Mortality
Associated with monoarticular
arthritis
0/73 (0)
10/69 (14)
Associated with polyarticular
arthritis
0/7 (0)
10/39 (26)
WBC count 111 ⫻ 109 cells/mm3
41/43 (95)
55/90 (61)
Gram stain
14/37 (38)
61/79 (77)
Culture
70/80 (88)
82/98 (84)
Positive results of testing of joint fluid
for Streptococcus pneumoniae
NOTE. n/N, no. of patients with finding or characteristic/no. of patients
for whom data were available; URTI, upper respiratory tract infection.
Major risk factors in adults included rheumatoid arthritis (22%), alcoholism (20%), osteoarthritis (14%), prosthetic
joints (14%), coronary disease (10%), corticosteroid use (9%),
and multiple myeloma or monoclonal gammopathy (8%). Risk
factors in children with pneumococcal septic arthritis included
sickle cell anemia (10%), hemophilia (9%), HIV infection (9%),
and X-linked agammaglobulinemia (3%).
Underlying focus of pneumococcal disease. The vast majority of children with pneumococcal septic arthritis (75 [94%]
of 80 children for whom adequate data were available) had no
underlying extra-articular pneumococcal infection. Three (4%)
of these 80 children had meningitis, and 2 (3%) had pneumonia. One-half of the adults with pneumococcal septic arthritis had no underlying extra-articular focus (53 [50%] of
105 adults for whom adequate data were available). Thirtyeight (36%) of these 105 adult patients had pneumococcal
pneumonia, 16 (15%) had meningitis, and 6 (6%) had endocarditis. Eight adult patients had 11 extra-articular site of
infection: 4 had pneumonia and meningitis, 2 had meningitis
and endocarditis, 1 had pneumonia and endocarditis, and 1
had pneumococcal pneumonia, endocarditis, and meningitis
(Austrian syndrome).
Predictors of mortality. The overall mortality was 19%
(20 of 108) among adults and 0% (0 of 82) in children. By
univariate analysis (x2 test), mortality was predicted by pneumococcal bacteremia (mortality was 24% among patients with
bacteremia [18 of 74 patients] and 6% among patients without
bacteremia [2 of 31 patients] for whom adequate data were
available; P p .03). Mortality was higher among patients 160
years old (26% [14 of 53 patients]) than among those ⭐60
years old (12% [6 of 51 patients]), but the difference was not
statistically significant (P p .06 ). Mortality was higher among
patients with polyarticular disease (26% [10 of 39 patients])
than among those with monoarticular disease (14% [10 of 69]),
but the difference was not statistically significant (P p .15).
Alcoholism, rheumatoid arthritis, invasive pneumococcal disease at another site, leukopenia, and leukocytosis did not predict higher mortality.
Therapy and outcomes. Of 108 adults with septic arthritis,
88 survived and 20 died. Survivors were treated with intravenous antibiotics for an average duration of 30.1 days, followed
by oral antibiotics for an average duration of 30.6 days. Four
patients with infected prosthetic joints were treated with indefinite oral antibiotic suppression (they were excluded from
the analysis of duration of therapy). Four patients in older series
were treated with intra-articular antibiotics.
Of the patients who survived, 40 patients (45%) were treated
with operative incision and drainage, 32 patients (36%) were
treated with arthrocentesis, and 13 patients (15%) were treated
with arthroscopic drainage. Functional outcomes and mortality
Table 3. Joint involvement in 190 patients (82 children and 108 adults) with pneumococcal septic
arthritis.
Adults,
no. (%)
Children,
no. (%)
35 (32)
17 (21)
Hip
8 (7)
20 (24)
Shoulder
7 (6)
6 (7)
Ankle
5 (5)
12 (15)
Elbow
3 (3)
15 (18)
Sacroiliac
3 (3)
3 (4)
Wrist
2 (2)
3 (4)
Sternoclavicular
2 (2)
0
Metatarsophalangeal
2 (2)
0
Type of involvement, joint
Monoarticular
Knee
Acromioclavicular
1 (1)
0
Metacarpophalangeal
1 (1)
0
Polyarticular
Total
39 (36)
108
6 (7)
82
Pneumococcal Septic Arthritis • CID 2003:36 (1 February) • 321
Table 4. Comorbid conditions and risk factors
in 108 adults with pneumococcal septic arthritis.
Condition or risk factor
Patients,
no. (%)
Rheumatoid arthritis
24 (22)
Alcoholism
22 (20)
None (otherwise healthy)
16 (15)
Osteoarthritis
15 (14)
Prosthetic joint
15 (14)
Coronary disease
11 (10)
Corticosteroid use
10 (9)
HIV infection
8 (7)
COPD
8 (7)
Malignancy
8 (7)
CHF
7 (6)
SLE, other vasculitis
7 (6)
Splenectomy
6 (6)
Multiple myeloma
6 (6)
Gout
5 (5)
Monoclonal gammopathy
3 (3)
Diabetes mellitus
3 (3)
Hemophilia
2 (2)
Bone marrow transplant
2 (2)
Active tuberculosis
2 (2)
Aseptic necrosis of hip
2 (2)
Unspecified immunodeficiency
2 (2)
Miscellaneousa
5 (5)
NOTE. CHF, congestive heart failure; COPD, chronic
obstructive pulmonary disease; SLE, systemic lupus erythematosus.
a
Miscellaneous conditions included clubfoot, hereditary
spherocytosis, epilepsy, sleep apnea, and malnutrition (1
patient each).
were similar among the 3 treatment groups. Three patients with
minimal effusions were treated without drainage, including 2
patients with sacroiliitis and 1 patient with metacarpophalangeal arthritis who received only antibiotic therapy, and all had
good outcomes [16, 33, 49].
Functional outcomes for adults with pneumococcal septic
arthritis were good. Fifty-seven (74%) of 77 surviving patients
for whom follow-up data were available regained baseline joint
function. Sixteen patients (21%) had mild limitation of range
of motion, without disability. Four patients (5%) had significant
disability involving destruction of at least 1 knee joint; a shoulder joint was destroyed in one of these patients and an elbow
in another [4, 30, 56]. Seven adults (9%) developed pneumococcal osteomyelitis.
All 82 children with pneumococcal septic arthritis survived.
They were treated with intravenous antibiotics for a mean of
16.4 days and with oral antibiotic therapy for a mean of 11.6
322 • CID 2003:36 (1 February) • Ross et al.
days. Eighteen of these children (22%) developed osteomyelitis.
Of 54 children for whom detailed treatment information was
available, 31 (57%) were treated with operative incision and
drainage; 19 (35%) were treated with arthrocentesis; and 2 (4%)
were treated with arthroscopy. In addition, 2 patients were
treated without drainage. Follow-up information was available
for 47 children: 38 (81%) of these children regained normal
joint function, 4 (9%) had mild or moderate restrictions of
joint range of motion but no significant disability, and 5 (11%)
had severe disability.
Prosthetic joints. Fourteen patients had pneumococcal infections of prosthetic joints [3, 8, 11, 25, 27, 31, 37, 53, 59],
including 2 of our previously unreported patients. Outcome
information was not available for 1 patient. Of the remaining
13 patients, 3 died of pneumococcal sepsis. All 3 patients who
died were women with infected hip prostheses and large thigh
abscesses whose conditions deteriorated after prosthesis removal and surgical drainage. (One of these was patient 11 in
our series, discussed below.) Two patients developed loosening
of the hip prostheses, which were removed and reimplanted
after long courses of intravenous antibiotics. One of these patients also had bilateral infection of knee prostheses, which were
drained and left in place. She continued to receive oral suppressive antibiotics. The remaining 8 patients, who did not have
abscesses, were cured with a combination of long-term antibiotics and drainage. Four of these patients were maintained
on indefinite suppression with oral penicillin.
DISCUSSION
Prevalence, and clinical and laboratory features. Our experience and review of the literature suggest that the pneumococcus is a relatively common cause of septic arthritis. At
Boston City Hospital in 1979–1994, S. pneumoniae accounted
for 3% of cases of bacterial septic arthritis (table 6). Data on
the etiology of septic arthritis from 9 large series [60–68] and
the present study indicate that S. pneumoniae is the third most
Table 5. Comorbid conditions in 70 children
with pneumococcal septic arthritis.
Condition
None (otherwise healthy)
Patients,
no. (%)
50 (71)
Sickle cell anemia
7 (10)
Hemophilia
6 (9)
HIV infection
6 (9)
X-linked agammaglobulinemia
2 (3)
Hereditary spherocytosis
1 (1)
Bone marrow transplantation
1 (1)
Unspecified immunodeficiency
1 (1)
Table 6. Species of 265 isolates from patients with septic arthritis at Boston City Hospital, 1979–1994.
Organism
Isolates,
no. (%)
Staphylococcus aureus
139 (52)
Staphylococcus epidermidis
25 (9)
Streptococcus pyogenes
22 (8)
Streptococcus agalactiae
9 (3)
Streptococcus pneumoniae
8 (3)
Neisseria gonorrhoeae
7 (3)
Haemophilus influenzae
4 (1)
Enterobacter cloacae
3 (1)
Escherichia coli
2 (!1)
Salmonella serotype Typhi
1 (!1)
Neisseria meningitidis
Polymicrobial infection
1 (!1)
22 (8)
Other streptococcal species
5 (2)
Other gram-negative bacilli
5 (2)
Miscellaneous
12 (4)
common pathogen in septic arthritis (after Staphylococcus aureus and Streptococcus pyogenes), causing 6% of cases (table 7).
Pneumococcal septic arthritis is equally common in men and
women. More boys than girls developed pneumococcal septic
arthritis, which is related to the higher incidence among young
men with hemophilic arthropathy and HIV disease. Gram
staining of synovial fluid found S. pneumoniae in 77% of adults
with pneumococcal septic arthritis, a frequency that is much
higher than the 33% of patients for whom Gram staining revealed other causes of bacterial septic arthritis [69].
Joint involvement. Joint involvement in adults with pneumococcal septic arthritis was similar to that in adults with septic
arthritis caused by other organisms [69]. Although Ispahani et
al. [3] found that the knee is involved less commonly in pneumococcal septic arthritis than in septic arthritis caused by other
organisms, we found that this joint is involved with similar
frequency if knee involvement in polyarticular disease is taken
into account. Other large joints, including the hip, shoulder,
elbow, and ankle, are occasionally infected.
In children with pneumococcal septic arthritis, hip involvement (24%) was most common, followed by knee (21%), elbow
(18%), and ankle (15%). This contrasts with bacterial arthritis
in children in general, in which knee involvement is seen in
35%–46% of patients [21, 70, 71], followed by hip, ankle, and
elbow involvement. (Involvement of large joints other than the
knee in septic arthritis is more common in children than in
adults.)
Polyarticular septic arthritis is more common in adults when
S. pneumoniae is the causative organism than when other bacteria are the cause. A total of 36% of cases of pneumococcal
septic arthritis in adults are polyarticular, compared with only
∼10%–20% of cases of bacterial arthritis caused by other pathogens [66, 69, 72]. This may be related to the high rate of
bacteremia among patients with pneumococcal septic arthritis.
Bacteremia was seen in 71% of adults (75 of 105 patients) with
pneumococcal septic arthritis reviewed in the present study,
compared with 27%–33% of patients with septic arthritis in
general [62, 69].
Comorbid conditions and risk factors. The major risk
factors for adult pneumococcal arthritis are rheumatoid arthritis and alcoholism. Alcohol increases the risk of aspiration
and upper airway bacterial colonization, decreases pulmonary
macrophage phagocytosis, and alters surfactant biochemistry
[73]. Alcoholism is implicated as a risk factor in up to 70% of
cases of pneumococcal bacteremia [74].
Rheumatoid arthritis predisposes to septic arthritis because
it is associated with increased synovial permeability, phagocytic
defects from drugs or disease, and skin breakdown and cellulitis
[75]. In one recent study, rheumatoid arthritis was the most
common risk factor for septic arthritis [66]. In rheumatoid
patients with septic arthritis, fever and leukocytosis are often
blunted or absent, resulting in delayed diagnosis, higher mortality, and worse functional outcomes [76]. Use of tumor necrosis factor antagonists to treat rheumatoid arthritis has recently been implicated in pneumococcal necrotizing fasciitis
and septic arthritis [59, 77]. Up to 59% of adults with septic
arthritis have underlying joint disorders [66]. In the present
series, ⭓1 joint disorder was seen in 52% of adults (56 of 108),
Table 7. Organisms isolated in 2407 cases of septic arthritis.
Organism
Isolates,
no. (%)
Staphylococcus aureus
1066 (44)
Streptococcus pyogenes
183 (8)
Streptococcus pneumoniae
156 (6)
Haemophilus influenzae
104 (4)
Mycobacterium tuberculosis
101 (4)
Escherichia coli
91 (4)
Coagulase-negative staphylococci
84 (3)
Neisseria gonorrhoeae
77 (3)
Streptococcus agalactiae
69 (3)
Pseudomonas aeruginosa
36 (1)
Neisseria meningitidis
28 (1)
Salmonella species
25 (1)
Other gram-negative rods
110 (5)
Other b-hemolytic streptococci
104 (4)
Polymicrobial
Fungi
4 (!1)
Miscellaneous
NOTE.
33 (1)
136 (6)
Data are from table 6 and [60–68].
Pneumococcal Septic Arthritis • CID 2003:36 (1 February) • 323
most commonly rheumatoid arthritis but also osteoarthritis,
prosthetic joints, gout, aseptic necrosis of the hip, and hemophilic arthropathy.
HIV infection was a risk factor for septic arthritis in 7% of
adults and 9% of children in the present series. This is not
surprising, given the frequency with which bacteremic pneumococcal infection occurs in HIV-positive patients [78] and
the presence of underlying hemophilic arthropathy in many.
Pneumococcal bacteremia and the pathogenesis of septic
arthritis. Septic arthritis is an uncommon complication of
pneumococcal bacteremia. We identified 1003 episodes of
pneumococcal bacteremia that occurred at Boston City Hospital in 1979–1994. Six episodes were complicated by septic
arthritis, an incidence of 0.6%. This is similar to rates reported
by other authors: 0.3% (1 case of arthritis in 325 episodes of
pneumococcal bacteremia) [79], 0.45% (2 cases in 444 episodes) [80], and 0.7% (2 of 294 patients) [78].
Septic arthritis usually arises from hematogenous seeding of
a joint. In many cases, a primary focus is not identified. For
S. aureus, the most common cause of septic arthritis, an extraarticular focus of staphylococcal infection is found in only 52%
of patients [62]. It has long been known that pneumococcal
arthritis may be “primary,” or not associated with extra-articular disease. Bulkley noted in 1914 [81] that 16% of cases of
pneumococcal septic arthritis were not associated with another
focus of pneumococcal disease. One-half of the patients with
pneumococcal septic arthritis reviewed here did not have an
underlying focus of pneumococcal disease, such as pneumonia
or meningitis. Presumably, septic arthritis arose from joint
seeding during transient bacteremia with a mucous membrane
source.
Children experience transient pneumococcal bacteremia
without an identifiable focus [82], but this phenomenon also
occurs in adults. In 12,000 South African gold miners followed
up for 4 years in a trial of pneumococcal vaccination, 217
episodes of pneumococcal bacteremia were documented.
Twenty-nine of these episodes (13%) were not associated with
focal infection, and 14 of these patients recovered without antimicrobial therapy [83]. In one study of pneumococcal bacteremia, 38 (9%) of 424 episodes that occurred in adults were
not associated with a specific source [80]. Bacteremia predicted
mortality in patients with pneumococcal septic arthritis. The
high mortality associated with pneumococcal bacteremia has
long been recognized [84] and has not decreased since 1960
[74, 85–88].
Prosthetic joints. Septic arthritis is 15 times more common
in prosthetic joints than in native joints [89], and up to 17%
of cases of septic arthritis occur in prosthetic joints [68]. The
mortality associated with pneumococcal septic arthritis of prosthetic joints (23% [3 of 13 adults]) was similar to the mortality
associated with pneumococcal arthritis of native joints (18%
324 • CID 2003:36 (1 February) • Ross et al.
[17 of 95 adults]). Of the 10 surviving patients, 9 were able to
retain at least 1 infected prosthetic joint; 5 of these patients
received long-term suppressive antibiotic therapy, although 4
were treated with shorter courses of antibiotics and did not
experience relapse.
Therapy and outcome. Our experience and the recent
report of James and Thomas [56] support administration of
courses of antibiotic therapy lasting a total of 3–4 weeks for
uncomplicated pneumococcal septic arthritis, including 1–2
weeks of intravenous therapy. Intra-articular antibiotics are no
longer recommended because of the potential for chemical synovitis [72].
The favorable outcomes seen in patients who survive pneumococcal septic arthritis were known in the preantibiotic era.
In 1939, Heffron [90] wrote that “provided treatment is undertaken early, complete return of joint function is to be expected.” A total of 95% of adults and 90% of children in our
review had a return to baseline joint function or mild limitation
of range of motion. By comparison, 150% of patients with
staphylococcal septic arthritis have serious residual joint damage [2]. In a recent study, 32% of all patients with septic arthritis
and 46% of patients with septic arthritis caused by S. aureus
had poor outcomes [67].
Outcomes were similar whether patients were treated with
surgical incision and drainage, arthrocentesis, or arthroscopic
drainage. Repeated needle aspirations are adequate for the initial drainage of infected joints. Surgical drainage is indicated
when patients do not respond to arthrocentesis, when loculated
joint fluid prevents adequate needle aspiration, or when the
hip joint is involved [1, 69, 72]. Some data indicate that outcomes may be worse in patients who undergo surgery for septic
arthritis, although this could be accounted for by the retrospective nature of the studies and the selection of more severely
affected patients for surgery [67, 91].
The 4 adults in the present review with poor outcomes all
had preexisting joint pathology (2 had rheumatoid arthritis, 1
had gout, and 1 had hemophilic arthropathy), and the diagnosis
of septic arthritis was delayed in 1 patient. Of the 5 children
with poor outcomes, 3 had septic arthritis of the hip, which is
strongly associated with worse outcomes in children [21].
Mortality among adults was 19%, 26% in those 160 years
old. This is comparable to the mortality of 14% associated with
nongonococcal arthritis in adults [62]. The mortality of bacterial septic arthritis is known to be age dependent, increasing
from 5% among those !65 years old to 32% among those ⭓65
years old [67]. We noted a lower mortality among adults (19%
compared with 32%) than was seen in the series by Ispahani
et al. [3]; this difference likely can be explained by the fact that
our patient population was younger. Only 53% of the patients
reviewed in our study were 160 years old, compared with 80%
in the other series.
Impact of antibiotic resistance. Since 1989, 7 children [45,
58, 92] and 4 adults [28, 46, 53] have been reported who had
penicillin-resistant pneumococcal septic arthritis. Of the 7 pediatric patients, 4 had strains of S. pneumoniae that were resistant to penicillin but sensitive to ceftriaxone, using current
breakpoints for nonmeningeal isolates; all patients were successfully treated with ceftriaxone or cefotaxime (1 patient also
received vancomycin). Three pediatric patients had strains with
high-level ceftriaxone resistance, and these patients responded
to vancomycin-containing regimens (one patient also received
ceftriaxone, and another also received clindamycin).
Three adults were infected with pneumococcal strains manifesting intermediate resistance to penicillin, and 1 patient
had a strain with high-level penicillin resistance and intermediate resistance to ceftriaxone. One patient whose infection
was intermediately resistant to penicillin was treated with penicillin alone, and another was treated with vancomycin and
rifampin, with good outcomes in both cases. (The regimens
for the other 2 patients were not specified, but both patients
achieved clinical cure.)
Patient 11 in our series was a 73-year-old woman who was
admitted to another facility with left lower lobe pneumonia.
Despite receiving cefuroxime therapy, she developed increasing right hip pain over the course of 10 days and was transferred to Boston Medical Center, where vancomycin therapy
was initiated. Examination revealed exquisite tenderness on
manipulation of the hip, with erythema, edema, and bulla
formation over the old right-hip arthroplasty scar. She was
taken to the operating room for arthroplasty removal and
debridement, with findings of a grossly infected hip prosthesis
and a pus collection from the anterior thigh to the knee.
Surgical wound cultures and blood cultures grew S. pneumoniae, with a penicillin MIC of 2 mg/mL (resistant), a ceftriaxone MIC of 2 mg/mL (intermediately resistant), and a
vancomycin MIC of 1 mg/mL (sensitive) by Etest. Postoperatively, the patient’s condition deteriorated, and she died as
a result of multisystem organ failure.
The clinical significance of penicillin resistance in the pneumococcus is unclear. In one study, mortality was not higher
among adults with pneumonia with strains of S. pneumoniae
that were resistant to penicillin and third-generation cephalosporins. However, few strains demonstrated high-level resistance, and some “cephalosporin-resistant” strains would not
be considered resistant by current breakpoints [93]. A recent
Canadian study did show an increase in mortality that was
associated with high-level pneumococcal b-lactam resistance
[94]. Pneumococcal serotyping was available for 38 isolates; 34
(89%) were represented in the 23-valent pneumococcal vaccine.
Many cases of pneumococcal septic arthritis are, therefore, potentially vaccine preventable.
Acknowledgments
We thank Kathy Browne, Megan Sandel, and Michael G.
Worthington for their assistance and support.
References
1. Smith JW, Hasan MS. Infectious arthritis. In: Mandell GL, Bennett JE,
Dolin R, eds. Mandell, Douglas and Bennett’s principles and practice
of infectious diseases. 5th ed. Philadelphia: Churchill Livingston, 2000:
1175–82.
2. Goldenberg DL, Reed JI. Medical progress: bacterial arthritis. N Engl
J Med 1985; 312:764–71.
3. Ispahani P, Weston VC, Turner DPJ, Donald FE. Septic arthritis due
to Streptococcus pneumoniae in Nottingham, United Kingdom, 1985–
1998. Clin Infect Dis 1999; 29:1450–4.
4. Dyer HR, Gum OB. Pneumococcal arthritis complicating rheumatoid
arthritis. South Med J 1966; 59:537–8.
5. Myers AH, Miller LM, Pinals RS. Pyarthrosis complicating rheumatoid
arthritis. Lancet 1969; 2:714–6.
6. Huskisson EC, Hart FD. Severe, unusual and recurrent infections in
rheumatoid arthritis. Ann Rheum Dis 1972; 31:118–21.
7. Kluge R, Schmidt M, Barth WF. Pneumococcal arthritis. Ann Rheum
Dis 1973; 32:21–4.
8. Mallory TH. Sepsis in total hip replacement following pneumococcal
pneumonia. J Bone Joint Surg Am 1973; 55:1753–4.
9. Torres J, Rathbun HK, Greenough WB III. Pneumococcal arthritis:
report of a case and review of the literature. Johns Hopkins Med J
1973; 132:234–41.
10. Kauffman CA, Watanakunakorn C, Phair JP. Pneumococcal arthritis.
J Rheumatol 1976; 3:409–19.
11. Ahlberg A, Carlsson AS, Lindberg L. Hematogenous infection in total
joint replacement. Clin Orthop 1978; 137:69–75.
12. Good AE, Gayes JM, Kauffman CA, Archer GL. Multiple pneumococcal
pyarthrosis complicating rheumatoid arthritis. South Med J 1978; 71:
502–4.
13. Chusid MJ, Sty JR. Pneumococcal arthritis and osteomyelitis in children. Clin Pediatr (Phila) 1981; 20:105–7.
14. Friedman RS, Perez HD, Goldstein IM. Septic arthritis of the sternoclavicular joint due to gram-positive microorganisms. Am J Med
Sci 1981; 282:91–3.
15. Andersen BR, Mayer ME, Geiseler PJ, Niebel JP. Multi-joint pneumococcal pyarthrosis in a patient with a chemotactic defect. Arthritis
Rheum 1983; 26:1160–2.
16. Kumar R, Balachandran S. Unilateral septic sacro-iliitis: importance of
the anterior view of the bone scan. Clin Nucl Med 1983; 8:413–5.
17. Hofmann A, Wyatt R, Bybee B. Septic arthritis of the knee in a 12year-old hemophiliac. J Pediatr Orthop 1984; 4:498–9.
18. Epstein JH, Zimmermann B, Ho G Jr. Polyarticular septic arthritis. J
Rheumatol 1986; 13:1105–7.
19. Fajardo JE, Mickunas VH, de Triquet JM. Suppurative arthritis and
hemophilia. Pediatr Infect Dis 1986; 5:593–4.
20. Syrogiannopoulos GA, McCracken GH Jr, Nelson JD. Osteoarticular
infections in children with sickle cell disease. Pediatrics 1986; 78:
1090–6.
21. Welkon CJ, Long SS, Fisher MC, Alburger PD. Pyogenic arthritis in
infants and children: a review of 95 cases. Pediatr Infect Dis 1986; 5:
669–76.
22. Hellerstein A, Wiedermann BL. Pneumococcal sacroiliitis in an infant.
Pediatr Infect Dis J 1987; 6:759–61.
23. Mba EC, Njoku OS. Polyarticular pneumococcal pyarthrosis in a young
haemophiliac. Acta Haematol 1987; 77:62–3.
24. Morley PK, Hull RG, Hall MA. Pneumococcal septic arthritis in rheumatoid arthritis. Ann Rheum Dis 1987; 46:482–4.
25. Ryczak M, Sands M, Brown RB, Sklar JH. Pneumococcal arthritis in
Pneumococcal Septic Arthritis • CID 2003:36 (1 February) • 325
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
a prosthetic knee: case report and review of the literature. Clin Orthop
1987; 224:224–7.
Selby C, Hart S, Ispahani P, Toghill PJ. Bacteraemia in adults after
splenectomy or splenic irradiation. Q J Med 1987; 63:523–30.
Sublett KL, Katz AL. Medical management of pneumococcal arthritis
involving a knee prosthesis. Arthritis Rheum 1987; 30:940–2.
Fullerton RC, McNabb PC. Community-acquired pneumonia and septic arthritis caused by penicillin-resistant pneumococci. J Tenn Med
Assoc 1989; 82:13–4.
Pappo AS, Buchanan GR, Johnson A. Septic arthritis in children with
hemophilia. Am J Dis Child 1989; 143:1226–8.
Ragni MV, Hanley EN. Septic arthritis in hemophilic patients and
infection with human immunodeficiency virus. Ann Intern Med 1989;
110:168–9.
Wollner A, Gilon D, Mattan Y, Rubinow A, Pogrund H. Pneumococcal
infection of a prosthetic hip joint. Int Orthop 1989; 13:135–6.
Bleasel JF, York JR, Rickard KA. Septic arthritis in human immunodeficiency virus–infected haemophiliacs. Br J Rheumatol 1990; 29:
494–6.
Bruyn GAW, Thompson J, Van der Meer JWM. Pneumococcal endocarditis in adult patients: a report of five cases and review of the
literature. Q J Med 1990; 74:33–40.
Brzeski M, Smart L, Baird D, Jackson R, Sturrock R. Pneumococcal
septic arthritis after splenectomy in Felty’s syndrome. Ann Rheum Dis
1991; 50:724–6.
Graham MP, Barzaga RA, Cunha BA. Pneumococcal septic arthritis of
the knee in a patient with multiple myeloma. Heart Lung 1991; 20:
416–8.
Jacobs NM. Pneumococcal osteomyelitis and arthritis in children. Am
J Dis Child 1991; 145:70–4.
Sanzen L. Spread of Streptococcus pneumoniae between artificial joints
in a rheumatoid patient. Acta Orthop Scand 1991; 62:597–8.
Cuesta M, Bernad M, Espinosa A, Herranz P, Mola EM, Baños JG.
Pneumococcal septic arthritis as the first manifestation of multiple
myeloma. Clin Exp Rheumatol 1992; 10:483–4.
Granowitz EV, Donaldson WR, Skolnik PR. Gas-forming soft tissue
abscess caused by Streptococcus pneumoniae. Am J Med 1992; 93:105–7.
Merchan ECR, Magallon M, Manso F, Martin-Villar J. Septic arthritis
in HIV-positive haemophiliacs. Int Orthop 1992; 16:302–6.
Aprin H, Turen C. Pyogenic sacroiliitis in children. Clin Orthop 1993;
287:98–106.
Schwella N, Schwerdtfeger R, Schmidt-Wolf I, Schmid H, Siegert W.
Pneumococcal arthritis after bone marrow transplantation. Bone Marrow Transplant 1993; 12:165–6.
Litwin MS, Kirkham BW. Polyarticular pneumococcal sepsis in rheumatoid arthritis. Aust NZ J Med 1994; 24:218–9.
Dahut W, Georgiadis M. Pneumococcal arthritis and functional asplenia after allogeneic bone marrow transplantation. Bone Marrow
Transplant 1995; 15:161.
Abbasi S, Orlicek SI, Almohsen I, Luedtke G, English BK. Septic arthritis and osteomyelitis caused by penicillin and cephalosporin-resistant Streptococcus pneumoniae in a children’s hospital. Pediatr Infect
Dis J 1996; 15:78–83.
Merle-Melet M, Tortuyaux JM, Condette S, Maurer P, Lion C, Boissel
P. Early post-splenectomy arthritis caused by penicillin-resistant Streptococcus pneumoniae. Eur J Clin Microbiol Infect Dis 1996; 15:159–60.
Korman TM, Brodie GN, Grayson ML. Pneumococcal arthritis and
monoclonal gammopathy of undetermined significance. Aust NZ J
Med 1997; 27:342.
Mordehai J, Kurzbart E, Cohen E, Mares AJ. Cyanotic limb in a newborn: a peculiar presentation of septic hip. Pediatr Emerg Care 1997;13:
408–9.
Pinson AG, Jolles PR, Balkissoon ARA. Pneumococcal sacroiliitis.
South Med J 1997; 90:649–52.
Saraux A, Taelman H, Blanche P, et al. HIV infection as a risk factor
for septic arthritis. Br J Rheumatol 1997; 36:333–7.
326 • CID 2003:36 (1 February) • Ross et al.
51. Arlievsky N, Li KI, Muñoz JL. Septic arthritis with osteomyelitis due
to Streptococcus pneumoniae in HIV-infected children. Clin Infect Dis
1998; 27:898–9.
52. O’Brien CM, Darley ESR, Kelly AJ, Nelson IW. Septic sacroiliitis: an
unusual causative organism in a rare condition. Int J Clin Pract 1998;
52:206–7.
53. Raad J, Peacock J. Septic arthritis due to Streptococcus pneumoniae:
report of four cases and review of the literature [abstract 65]. Clin
Infect Dis 1998; 27:932.
54. Lohse A, Despaux J, Auge B, Toussirot E, Wendling D. Pneumococcal
polyarticular septic arthritis in a patient with rheumatoid arthritis. Rev
Rhum Engl Ed 1999; 66:344–6.
55. Oliker R, Cuhna B. Streptococcus pneumoniae septic arthritis and osteomyelitis in an HIV-seropositive patient. Heart Lung 1999; 28:74–5.
56. James PA, Thomas MG. Streptococcus pneumoniae septic arthritis in
adults. Scand J Infect Dis 2000; 32:491–4.
57. Peters TR, Brumbaugh DE, Lawton AR, Crowe JE Jr. Recurrent pneumococcal septic arthritis as the presenting manifestation of X-linked
agammaglobulinemia. Clin Infect Dis 2000; 31:1287–8.
58. Lane JE, Moore CC, Beckish ML, Stephens JL. Isolated septic arthritis
caused by penicillin-resistant Streptococcus pneumoniae. South Med J
2001; 94:429–31.
59. Baghai M, Osmon DR, Wolk DM, Wold LE, Haidukewych GJ, Matteson EL. Fatal sepsis in a patient with rheumatoid arthritis treated with
etanercept. Mayo Clin Proc 2001; 76:653–6.
60. Ryan MJ, Kavanagh R, Wall PG, Hazleman BL. Bacterial joint infections
for England and Wales: analysis of bacterial isolates over a four year
period. Br J Rheumatol 1997; 36:370–3.
61. Goldenberg DL, Cohen AS. Acute infectious arthritis. Am J Med
1976; 60:369–77.
62. Sharp JT, Lidsky MD, Duffy J, Duncan MW. Infectious arthritis. Arch
Intern Med 1979; 139:1125–30.
63. Ho G, Su EY. Therapy for septic arthritis. JAMA 1982; 247:797–800.
64. Cooper C, Cawley MI. Bacterial arthritis in an English health district:
a 10 year review. Ann Rheum Dis 1986; 45:458–63.
65. McCutchan HJ, Fisher RC. Synovial leukocytosis in infectious arthritis.
Clin Orthop 1990; 257:226–30.
66. Kaandorp CJ, Dinant HJ, van de Laar MA, Moens HJ, Prins AP, Dijkmans
BA. Incidence and sources of native and prosthetic joint infection: a
community based prospective survey. Ann Rheum Dis 1997; 56:470–5.
67. Weston VC, Jones AC, Bradbury N, Fawthorp F, Doherty M. Clinical
features and outcome of septic arthritis in a single UK Health District
1982–1991. Ann Rheum Dis 1999; 58:214–9.
68. Dubost JJ, Saubrier M, De Champs C, Ristori JM, Bussière JL, Sauvezie
B. No changes in the distribution of organisms responsible for septic
arthritis over a 20 year period. Ann Rheum Dis 2002; 61:267–9.
69. Smith JW, Piercy EA. Infectious arthritis. Clin Infect Dis 1995; 20:
225–31.
70. Nelson JD. The bacterial etiology and antibiotic management of septic
arthritis in infants and children. Pediatrics 1972; 50:437–40.
71. Krogstad P, Smith AL. Osteomyelitis and septic arthritis. In: Feigin RD,
Cherry JD, eds. Textbook of pediatric infectious disease. 4th ed. Philadelphia: WB Saunders, 1998:683–704.
72. Pioro MH, Mandell BF. Septic arthritis. Rheum Dis Clin North Am
1997; 23:239–58.
73. MacGregor RR, Louria DB. Alcohol and infection. Curr Clin Top Infect
Dis 1997; 17:291–315.
74. Hook EW III, Horton CA, Schaberg DR. Failure of intensive care unit
support to influence mortality from pneumococcal bacteremia. JAMA
1983; 249:1055–7.
75. Gardner GC, Weisman MH. Pyarthrosis in patients with rheumatoid
arthritis: a report of 13 cases and a review of the literature from the
past 40 years. Am J Med 1990; 88:503–11.
76. Blackburn WD, Dunn TL, Alarcón GS. Infection versus disease activity
in rheumatoid arthritis: eight years’ experience. South Med J 1986; 79:
1238–41.
77. Murphy MA, Nasraway S, McGovern B. Pneumococcal necrotizing
fasciitis in a rheumatoid arthritis patient treated with etanercept [abstract 137]. Clin Infect Dis 2001; 33:1112.
78. Redd SC, Rutherford GW III, Sande MA, et al. The role of human
immunodeficiency virus infection in pneumococcal bacteremia in San
Francisco residents. J Infect Dis 1990; 162:1012–7.
79. Gransden WR, Eykin SJ, Phillips I. Pneumococcal bacteraemia: 325
episodes diagnosed at St. Thomas’s Hospital. Br Med J (Clin Res Ed)
1985; 290:505–8.
80. Burman LÅ, Norrby R, Trollfors B. Invasive pneumococcal infections:
incidence, predisposing factors, and prognosis. Rev Infect Dis 1985; 7:
133–42.
81. Bulkley K. Pneumococcic arthritis. Ann Surg 1914; 59:71–100.
82. Burke JP, Klein JO, Gezon HM, Finland M. Pneumococcal bacteremia:
review of 111 cases, 1957–1969, with special reference to cases of undetermined focus. Am J Dis Child 1971; 121:353–9.
83. Austrian R. Life with the pneumococcus. Philadelphia: University of
Pennsylvania Press, 1985:30–1.
84. Tilghman RC, Finland M. Clinical significance of bacteremia in pneumococcic pneumonia. Arch Intern Med 1937; 59:602–19.
85. Austrian R, Gold J. Pneumococcal bacteremia with especial reference
to bacteremic pneumococcal pneumonia. Ann Intern Med 1960; 60:
759–76.
86. Plouffe JF, Breiman RF, Facklam RR. Bacteremia with Streptococcus
pneumoniae: implications for therapy and prevention. JAMA 1996;
275:194–8.
87. Afessa B, Greaves WL, Frederick WR. Pneumococcal bacteremia in
adults: a 14-year experience in an inner-city university hospital. Clin
Infect Dis 1995; 21:345–51.
88. Watanakunakorn C, Bailey TA. Adult bacteremic pneumococcal pneumonia in a teaching hospital. Arch Intern Med 1997; 157:1965–71.
89. Kaandorp CJ, Schaardenburg D, Krijnen P, Habbema JD, van de Laar
MA. Risk factors for septic arthritis in patients with joint disease: a
prospective study. Arthritis Rheum 1995; 38:1819–25.
90. Heffron R. Pneumonia, with special reference to pneumococcal lobar
pneumonia. New York: Commonwealth Fund, 1939. Reprint. Cambridge, MA: Harvard University Press, 1979.
91. Broy SB, Schmid FR. A comparison of medical drainage (needle aspiration) and surgical drainage (arthrotomy or arthroscopy) in the
initial treatment of infected joints. Clin Rheum Dis 1986; 12:501–22.
92. Kaplan SL, Mason EO, Barson WJ, et al. Outcome of invasive infections
outside the central nervous system caused by Streptococcus pneumoniae
nonsusceptible to ceftriaxone in children treated with beta-lactam antibiotics. Pediatr Infect Dis J 2001; 20:392–6.
93. Pallares R, Liñares J, Vadillo M, et al. Resistance to penicillin and
cephalosporin and mortality from severe pneumococcal pneumonia in
Barcelona, Spain. N Engl J Med 1995; 333:474–80.
94. Feikin DR, Schuchat A, Kolczak M, et al. Mortality from invasive
pneumococcal pneumonia in the era of antibiotic resistance. Am J
Public Health 2000; 90:223–9.
Pneumococcal Septic Arthritis • CID 2003:36 (1 February) • 327